Exposure to intimate violence is a pervasive stressor associated with adverse impact on womens'psycholological and physical health. No prospective study has examined whether the prevalent and often severe stressor of intimate violence is associated with cardiovascular disease (CVD) events. We propose to examine type of abuse (physical, sexual or emotional) and lifestage at abuse (childhood, adolescence, or adulthood) as predictors of incident hypertension, hypercholesterolemia, diabetes, and CVD events in a prospective cohort of 68,518 women who answered a detailed lifetime abuse questionnaire in 2001 as participants in the Nurses'Health Study II. Preliminary retrospective data from this cohort show dose- response associations of abuse exposures with CVD risk factors, myocardial infarction, and stroke. Primary aims will test the associations of emotional, physical and sexual abuse with incident coronary heart disease, stroke, type 2 diabetes mellitus, hypertension, and hypercholesterolemia. Secondary aims will explore whether polymorphisms in the glucocorticoid receptor, tumor necrosis factor alpha (TNFa), serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) genes interact with abuse history to alter CVD risk in women. We have collected abuse histories from 68,518 participants who are now being followed prospectively for incident disease events, making this the largest cohort ever assembled to examine the impact of abuse. We have also collected data on social support, coping style, depressive symptoms, socioeconomic position, and lifestyle risk factors for CVD, which will permit us to explore issues of confounding and effect modification. The ongoing NHSII cohort presents an ideal population and working infrastructure to facilitate the carrying out of the proposed studies at relatively low cost. The availability of biological samples already collected allows us to examine gene by environment interactions cost-effectively.